tbuckley/cabot-search huggingface dataset:
Association of biomarkers (BMs) with efficacy of adjuvant nivolumab (NIVO) vs placebo (PBO) in patients with resected stage IIB/C melanoma (CA209-76K).
Authors: Georgina V. Long, John M. M. Kirkwood, Christoph Hoeller, Jean-Jacques Grob, Jeffrey S. Weber, Janis M. Taube, Peter Mohr, Alexander Christopher Jonathan Van Akkooi, Carmen Loquai, Caroline Dutriaux, Vanna Chiarion-Sileni, Daniel J. Tenney, Sonia Dolfi, Hao Tang, Corey Ritchings, Maurice Lobo, Federico Campigotto, Wenjia Wang, Brian Gastman, Michele Del Vecchio
Journal: Journal of Clinical Oncology (2023)

9504 Background: Adjuvant NIVO significantly prolonged recurrence-free survival (RFS) over PBO in stage IIB/C melanoma in the randomized, phase III Checkmate 76K trial (HR; 95% CI: 0.42 [0.30–0.59]). For the first time, select BMs and their association with RFS were analyzed in early-stage melanoma treated with an anti-PD-1 agent. Methods: Baseline primary tumor and serum BMs were analyzed, including interferon gamma-related gene expression signature (IFNγ-sig), TMB, BRAF mutation, % intratumoral CD8+ T cells, tumor cell PD-L1 expression, and serum CRP levels. BMs were evaluated as continuous variables (high vs low levels) and dichotomized by median or prespecified cutoffs. HRs were estimated using a Cox proportional hazards model. Results: Analysis of continuous BM levels within treatment arms showed that higher IFNγ-sig, TMB, and % CD8+ T cells, and lower CRP levels were associated with prolonged RFS with NIVO but not PBO. The same trend was observed in the dichotomized analyses. No clear association between PD-L1 expression and RFS was identified in either arm. Benefit of NIVO over PBO was seen across all BM subgroups, including by BRAF V600 mutation status. Patients with higher IFNγ-sig, TMB, and % CD8+ T cells, and lower CRP levels showed numerically greater relative benefit with NIVO, although CIs overlapped (Table). Conclusions: Higher IFNγ-sig, TMB, and % CD8+ T cells, and lower CRP levels were associated with longer RFS with NIVO treatment. No BMs assessed were prognostic for RFS in the PBO arm, in contrast to previous reports in melanoma. Prolonged RFS was seen in patients treated with NIVO over PBO across levels of BMs, and irrespective of BRAF mutational status. Composite analyses of BMs with clinical and histopathologic factors will be evaluated for their potential to optimize risk:benefit stratification for NIVO in this patient population. Clinical trial information: NCT04099251 . [Table: see text]
Real world assessment of clinical benefit with consolidation durvalumab following chemoradiotherapy in stage III unresectable non-small cell lung cancer.
Authors: Shanthi Marur, Mark Mangurian, Corey Wise, Melissa Pozotrigo, Shika Marur, Andrew D. Norden, Andrew Toler, Laura Rose Bobolts
Journal: Journal of Clinical Oncology (2023)

e18853 Background: The phase III PACIFIC trial compared the efficacy of consolidation durvalumab to placebo in newly diagnosed, unresectable stage III non-small cell lung cancer (NSCLC) who had not progressed after chemoradiotherapy (CRT). With a median follow-up of 34.2 months, the median progression free survival (PFS) was 16.9 months (13.0-23.9) compared to 5.6 months (4.6-7.7) for placebo (HR = 0.55, 95% CI,0.45-0.68). We report a real-world study that utilizes surrogate endpoints to assess duration of clinical benefit with consolidation durvalumab. Methods: OncoHealth, a digital health company, conducted a retrospective observational real-world study to assess time to treatment failure in patients with unresectable Stage III NSCLC who received consolidation durvalumab after completion of CRT between June 2018-June 2021. Data sources included electronic medical records (EMR) submitted with prior authorization (PA) requests to OncoHealth and medical claims data. With a data cut-off of 12/22/2022, real-world Time to Progression (rwTTP), and real-world Time to Next Treatment (rwTTNT) were evaluated to assess time to treatment failure. All end points were measured from durvalumab administration dates, rwTTP spanned until earliest date of clinician-assessed progression, and rwTTNT spanned until initiation of subsequent treatment. Results: Total of 281 patients with unresectable Stage III NSCLC who received durvalumab after completion of definitive CRT were identified. Median age was 71 years (range: 53 to 88), 57% male, 53% former smokers, 47% Stage IIIA, 52% non-squamous histology and 98% received concomitant platinum-based chemotherapy prior to durvalumab. Median time between completing CRT and initiating durvalumab was 41 days. With a cutoff date of 12/22/2022, and a median follow up of 28.4 months, 34% (n = 95) experienced disease progression. Sites of progression included lung, lymph nodes, adrenal, liver, bone and brain. The median rwTTP was 10.6 months (range: 2.0-38.1 months) and median rwTTNT was 12.4 months (range: 2.5-39.6 months). Conclusions: In this real-world study, the patient and disease characteristics available in EMR were comparable to those reported in the PACIFIC trial. The rwTTP and rwTTNT reported here suggest treatment failure occurred within one year of exposure to durvalumab and subsequent line of treatment was initiated shortly thereafter. Variables such as co-morbidities, performance status, treatment compliance, change of payers and barriers to treatment in real world will be further explored.
End-of-life outcomes of patients with advanced cancer enrolled in palliative care.
Authors: Andrew Lynch, Liisa Lyon, Nirmala D. Ramalingam, Hannah Whitehead, Mina Chang, Raymond Liu
Journal: Journal of Clinical Oncology (2023)

12030 Background: Palliative Care (PC) integration improves end-of-life (EOL) outcomes for patients with advanced cancer. However, there is limited evidence in real world settings of the impact of PC enrollment on EOL outcomes and the presence of racial disparities in PC enrollment. We sought to understand how PC enrollment differs between certain patient demographics and whether enrollment affects EOL outcomes in a large integrated health system. Methods: This retrospective cross-sectional study included adults 18 years and older diagnosed with Stage IV solid cancers who died within 1 year of diagnosis at 21 cancer centers within Kaiser Permanente Northern California between 2018-2020. Demographics, clinical variables and EOL outcomes were compared by PC enrollment status. Categorical and continuous comparisons were made using Chi-squared and t-tests, respectively. Results: Among 3,575 patients diagnosed with stage IV solid cancers who died within 1 year of diagnosis (mean age 73.2), 52.8% were male; 8.2% were Black, 11.0% Hispanic, 12.3% Asian, and 67.7% non-Hispanic White. Most patients (93.0%) selected English as their preferred language. The most common cancer subtypes were thoracic (33.2%), upper GI (32.4%), and lower GI (10.6%). Overall, 1613 patients (45.1%) were enrolled in PC. Baseline demographics were similar between the PC and no-PC groups including gender (p = 0.58), race (p = 0.32), and preferred language (p = 0.23). There was a difference in mean age between groups (72.0 vs. 74.2, p &lt; 0.01). Patients enrolled in PC were more likely to enroll in hospice (42.9% vs. 25.7%, p &lt; 0.01, Table) and less likely to be hospitalized in the last 30 days of life (35.5% vs. 45.7%, p &lt; 0.01, Table). Short hospice stays (&lt; 3 days) were uncommon in both groups, and there was no statistically significant difference between groups (4.5% vs. 5.4%, p = 0.49, Table). There was no significant difference in the proportion of patients with multiple ED visits in the last 30 days of life between groups (21.0% vs. 21.8%, p = 0.56, Table). Conclusions: PC enrollment is associated with significant improvement in some EOL outcomes with higher rates of hospice enrollment and lower rates of hospitalization at the EOL. These outcomes were seen without racial disparities in PC enrollment. Future studies are needed to assess other outcomes related to goal-concordant care and to determine which patients benefit most from PC enrollment. [Table: see text]
Safety and efficacy of naxitamab plus modified dosing of GM-CSF for patients with high-risk neuroblastoma (HR-NB) in first complete remission (CR) or with primary refractory disease.
Authors: Brian H. Kushner, Shakeel Modak, Ellen M. Basu, Fiorella Iglesias Cardenas, Kim Kramer, Stephen S. Roberts, Nai-Kong V. Cheung
Journal: Journal of Clinical Oncology (2023)

e22012 Background: In an international trial, the humanized anti-GD2 antibody naxitamab+GM-CSF was effective against chemo-resistant HR-NB, leading to approval by the Food and Drug Administration. We subsequently modified GM-CSF dosing based on a shortened priming period and pharmacokinetics showing prolonged T½ of naxitamab. We investigated safety and efficacy of naxitamab plus GM-CSF administered by a novel schedule in HR-NB patients treated in 1 st CR (Group 1) or with primary refractory disease in bones and/or bone marrow (BM) (Group 2). Methods: Immunotherapy was administered q1-2 months up to 5 cycles in Group 1 and ≥5 cycles after major responses in Group 2. Naxitamab was infused intravenously (30-90”) on days 1/Monday-3/Wednesday-5/Friday (i.e., 3 doses/cycle), 3mg/kg/infusion (9mg/kg/cycle, i.e., ~270mg/m 2 /cycle). Previously, priming doses of GM-CSF 250µg/m 2 /day were subcutaneously-administered x5 (days -4 to 0), followed by a step-up to 500µg/m 2 /day x5 (days 1-to-5), but now priming doses were x3 days (days -2 to 0 [Friday-Saturday-Sunday]) and stepped-up dosing was x7 (days 1-to-7 [Monday-to-Sunday]), i.e., through 2 days after the last dose of naxitamab. Patients did not receive isotretinoin. Follow-up was from start of naxitamab through 1/15/23. Results: From 2/22/2021-to-12/15/22, 59 patients (32 Group 1, 27 Group 2) received 1-10 (median 5) cycles, total 250. No unexpected toxicities occurred. No patient had to discontinue GM-CSF. Treatment was outpatient, except 3 patients with hypertension. Cycles were aborted because of viral symptoms (n=3), suspected small bowel obstruction (n=3), hypoxia (n=2), and hyperbilirubinemia (n=1). Four patients received only ½ of dose 1 in cycle 1 because of agitation or hypotension. In Group 1, 4/32 patients relapsed at 4-5 months while 28 patients remain in CR at 1+-to-22+ (median 15+) months. In Group 2, disease sites and responses were: BM alone (n=7): CR in 6 (1 later relapsed); MIBG alone (Curie scores 1-11) (n=8): 1 partial response, 1 progressive disease, 2 stable (1 later relapsed), 4 non-evaluable because of radiotherapy; MIBG (Curie scores 1-26) and BM(+) (n=12): 7 CR (3 later relapsed), 4 PR, 1 stable disease (subsequently progressed). Conclusions: This large experience confirms that the new schedule is safe and, despite short follow-up, appears as effective as the prior schedule.
Sexual dysfunction in patients with cancer: Results from the CLARIFY project.
Authors: Aylen Vanessa Ospina Serrano, Constanza Maximiano, Blanca Cantos Sanchez de Ibarguren, Maria Torrente, Miriam Mendez, Juan Cristobal Sanchez, Virginia Calvo, Ana Collazo Lorduy, Mariola Blanco, Beatriz Nuñez García, Ivan Triana, Consuelo Parejo, Paula Martinez, Narjust Florez, Mariano Provencio-Pulla
Journal: Journal of Clinical Oncology (2023)

12094 Background: Survivors patients with cancer may suffer long-term consequences related to antineoplastic treatments and tumor itself, leading to deterioration of quality of life and resulting in disturbances including sexual dysfunction (SD). We aimed to identify and characterize SD in a cohort of Spanish patients. Methods: Analytical observational study in patients included in the CLARIFY H2020 project at the Hospital Universitario Puerta de Hierro. From October 2020 to May 2022, clinical and demographic variables were collected as well as measures of sexual function using a validated Spanish-language, gender-targeted separately questionnaire. A descriptive domain on frequency of sexual activity during the last four weeks (DFSA) and multiple domains assessing phases of sexual response (DESR), according to DSM IV and DSM V parameters including desire, arousal, lubrication, orgasm, satisfaction with sexual performance, global sexual satisfaction, anticipatory anxiety and sexual initiative were evaluated. Descriptive, trend associations and logistic regression analyses were performed. Results: 383 patients were included, cancer type distribution was breast cancer 68.14% (261), lung cancer 26.37% (101) and lymphomas 5.50% (21). The average age was 56.5 years (range 33-88). 19.58% (75) of patients were men and 80.42% (308) woman. 69% of men and 31% of women reported they were sexually active. The absolute frequency of Global sexual dissatisfaction (GSD) was 76% in women and 24% in men, according to neoplasia; GSD was 36% in patients with early breast cancer, 14% in men with lymphoma, and 9% in men with lung cancer. Women with metastatic breast cancer presented the highest tendency to have severe disorders of DESR. In multinomial logistic regression, significant associations were found in women with metastatic breast cancer and severe disorders of: arousal (p 0.000), lubrication (p 0.002) orgasm (p 0.000), as well as dissatisfaction with sexual performance (p 0.000) and global sexual dissatisfaction (p 0.000). On the other hand, in women with lung cancer, severe arousal disorder (p 0.016) and global sexual dissatisfaction (p 0.044) were observed. Table. Conclusions: In our study, cancer survivors have high prevalence of SD related with oncological treatment and clinical characteristics of malignancy, being women the most affected population. Efforts should be made to support SD during follow-up to improve the quality of life of this growing oncologic population. [Table: see text]
Feasibility of daily physical activity monitoring and associations with treatment toxicity in older adults with metastatic prostate cancer.
Authors: Gregory Feng, Milothy Parthipan, Henriette Breunis, Narhari Timilshina, Enrique Soto Pérez de Celis, Daniel Santa Mina, Urban Emmenegger, Aaron Richard Hansen, Antonio Finelli, George Tomlinson, Monika K. Krzyzanowska, Andrew Matthew, Hance Clarke, Martine Puts, Shabbir M.H. Alibhai
Journal: Journal of Clinical Oncology (2023)

12055 Background: Accelerometry research suggests physical activity may be associated with treatment toxicity, but generalizability to geriatric oncology is unclear. As many older adults have low levels of physical activity and technology use, further exploration is warranted. This study explores the feasibility of daily physical activity monitoring and the association between step counts and symptoms. Methods: Older adults aged 65+ starting treatment (chemotherapy, enzalutamide/abiraterone, or Radium-223) for metastatic prostate cancer were enrolled in a prospective cohort study. Participants reported step counts (measured via smartphone and a free commercial app) and symptoms (Edmonton Symptom Assessment Scale (ESAS)) daily for their first treatment cycle (~1 month). The feasibility of daily monitoring was assessed with descriptive statistics and thematic analysis. The association between a 15% decline in steps (compared to pre-treatment baseline) and the emergence of moderate-to-severe symptoms and pain (ESAS ≥4) in the next 24 hours was assessed using logistic regression. The utility of a 15% step count decline in predicting the development of moderate-to-severe symptoms and pain was evaluated using sensitivity and positive predictive value (PPV). Results: Of 90 participants, 47 engaged in step count monitoring (mean age 75y; 52.2% participation rate). Daily physical activity monitoring was found to be feasible (90.5% median response rate; 94% retention rate) with numerous patient-reported benefits including increased self-awareness and motivation to engage in physical activity. During the first treatment cycle, instances of a 15% decline in steps were common (n=37, 78.7%), as was the emergence of moderate-to-severe symptoms overall (n=40, 85.1%) and pain (n=26, 55.3%). Overall, daily physical activity did not appear to be significantly predictive of symptoms (OR=1.8, 95% CI=0.42-7.74) overall or pain (OR=0.95, 95% CI=0.22-3.81). Predictive validity estimates revealed reasonable sensitivity for both moderate to severe symptoms overall (sensitivity=88.8%, 95% CI=68.7-95.0; PPV=73.0%, 95% CI=58.7-87.3) but poor PPV for pain (sensitivity=77.8%, 95% CI=58.6-97.0; PPV=37.8%, 95% CI=22.2-53.5). Conclusions: Despite recent studies framing physical activity changes as predictive of toxicity, PPV was only poor to fair. However, daily activity monitoring in older cancer patients appears feasible and may have other uses. Clinical trial information: NCT04193657 .
Genomic profiling in advanced NSCLC in Italy: First results of NERoNE (NSCLC Emilia Romagna Next Generation Sequencing Evaluation) project.
Authors: Federica Bertolini, Giulia Alberti, Elisabetta Petracci, Stefania Bettelli, Paola Ulivi, Paola Cravero, Giorgia Guaitoli, Francesca Zanelli, Marco Angelo Burgio, Kalliopi Andrikou, Maria Pagano, Alberto Verlicchi, Daniele Calistri, Michele Flospergher, Luciana Mastrodomenico, Michela Maur, Katia Di Emidio, Massimo Dominici, Carmine Pinto, Angelo Delmonte
Journal: Journal of Clinical Oncology (2023)

e21077 Background: The NERoNE Project evaluates the use of Next Generation Sequencing (NGS) in molecular profiling of advanced NSCLC (aNSCLC) patients (pts) in three Oncology Units (OU) of Emilia Romagna Region aiming to clarify the impact of such extensive tool in characterizing different NSCLC subpopulations. Methods: Since January 2020 to December 2022, 970 sequential aNSCLC pts from three OU (AUSL-IRCCS of Reggio Emilia, Modena University Hospital and IRST Meldola) were profiled by NGS. Samples from Modena and Reggio Emilia were analyzed at Modena University Hospital Molecular Pathology Lab using Myriapod IL- 56G, Cancer Panel DNA, Cancer Panel RNA, Oncomine DX Target Test Assay, Oncomine Focus Assay. Samples from IRST Meldola were processed at its Molecular Diagnostic Unit by Myriapod NGS cancer panel DNA e RNA, Oncomine Focus Assay and Oncomine Comprehensive Assay v3.We considered molecular alterations with available target therapies in Italy: EGFR mutations (mut) (exon 18,19,20,21), KRAS mut, BRAF V600E mut, ALK, ROS1, RET and NTRK rearrangements, MET exon 14 skipping mut, ErbB2 mut, FGFR 1-3 mut. PDL1 expression was assessed by standard immunohistochemistry on 486 pts. Results: Among 970 pts, 501 with at least one mut (52%) were considered for analysis: 266 were female (53%), mean age was 69 ± 11 years (min-max: 33-94) and 473 pts (94%) had adenocarcinoma. Molecular features are listed in table 1. Distribution of mut among ages, categorized as &lt; 60, 60-70 and &gt; 70 y, was similar, EGFR activating mut were most prevalent in females; KRAS mut (G12C and non G12C) were most prevalent in males; 41 pts had co-mutations (8.2%): the most frequent co-mut were EGFR mut (27%). PDL1 expression was &lt; 1% 129 (27%), 1-49% 211 (43,4%) and ≥50% 146 pts (30%). The majority of pts with EGFR activating mut had PDL1 &lt; 50%. Conclusions: NERoNE evaluates data from NGS profiling of three OU mapping key actionable molecular alterations in a large population of aNSCLC also accounting for PDL1 status. This preliminary analysis will be the starting point for further evaluations in order to improve the personalized approach to aNSCLC. [Table: see text]
Safety and efficacy of stereotactic body radiotherapy (SBRT) to oligoresidual sites combine with osimertinib in stage IV EGFR mutant NSCLC patients: A prospective pilot study.
Authors: Cheng Chen, Ying Wang, Siqin Liao, Bin Zheng, Chen Chen, Bangwei Zeng, Lianming Liao, Benhua Xu, Chun Chen
Journal: Journal of Clinical Oncology (2023)

e21069 Background: Presently osimertinib is used as first-line therapy in stage IV EGFR mutation NSCLC patients. Unfortunately, acquired resistance gradually develops, resulting in disease progression in most patients after 1 to 2 years. A retrospective study demonstrates that similar to the first- and second-generation EGFR-TKIs, half of the patients experienced failure within the residual disease. Consolidative local therapy had been evaluated as a promising strategy to improve PFS and delayed the appearance of new metastatic lesions in the pre-osimertinib era. It is intriguing to hypothesize that new distant metastases may arise from drug-resistant tumor cells at the residual tumor lesions. Therefore, compared to the salvage SBRT, preemptive consolidative SBRT to all oligo-residual tumor sites could potentially prevent recurrence and improve survival. Of note, this proposal is challenging because both EGFR-TKI and thoracic radiation have a detrimental effect on pulmonary interstitial tissue. Two retrospective studies had reported severe pneumonitis with radiotherapy plus osimertinib. Therefore, the potential toxicity profile needs to evaluate prospectively. Therefore, we performed this preliminary trial (ChiCTR2100053807) to evaluate the safety of consolidation SBRT at maximal osimertinib response. Methods: Patients were enrolled if residual metastasis was limited to five sites. Consolidative SBRT was initiated to all residual sites with different doses (30–50Gy) and fractions (3-10) when maximal tumor shrinkage was achieved with osimertinib. The primary endpoint was an adverse reaction defined by the Common Terminology Criteria for Adverse Events, version 4.0. Results: 5 consecutive patients were enrolled between December 2021 and December 2022. 80% of their residual disease was located in the lungs and lymph nodes, which constituted targets for thoracic SBRT. The median time to maximal response was 3 months (range, 2-6). The median follow-up time from consolidative SBRT was 6 months（range,6-12）. The most common grade 1-2 adverse events included leukopenia (60%, n = 3), anorexia (40%, n = 2), lymphopenia (40%, n = 2), paronychia (40%, n = 2), rash (40%, n = 2), which were thought to be likely related to osimertinib. One patient suffered from grade 1 pulmonary fibrosis at 16 months after SBRT. There was no Grade 3/4 acute and late radiation toxicity. So far, no disease progression occur with a median follow-up time of 18 months（range, 13-19）. Conclusions: This pilot studydemonstrated concurrent treatment with osimertinib and SBRT for the oligo-residue disease at TKI maximum response was well tolerated. Future prospective, randomized studies are desirable to confirm these preliminary findings. Clinical trial information: ChiCTR2100053807 .